The invention relates to an apparatus for and method of dispensing liquid. More especially, but not exclusively, the invention relates to dispensing liquid from well plates as widely used in the field of chemistry and biotechnology for microarraying and other applications.
Microarraying is a technique in widespread use. Conventional microarraying is based on standard multi-well plates having a 4.5 mm grid and 384 wells. However, larger array sizes of 1536 wells are becoming more widely used, these larger arrays conform to a 2.25 mm grid. Liquid samples are stored in the wells of a well plate. The liquid may be assays or any other biological or chemical sample of interest. To spot the liquid from a well, a pin is dipped in the well to retrieve an amount of the liquid. The pin carrying an amount of the sample liquid is then moved across to a spotting surface of a microscope slide or other suitable surface. A spot of liquid is deposited on the slide by bringing the pin into close proximity, or by physically contacting the tip of the pin, with the slide surface.
FIG. 1A of the accompanying drawings shows schematically a pin 110 conventionally used for spotting. The pin is in the form of a split pin, with liquid 111 being attracted to and carried on the pin by capillary action. The liquid is discharged from the pin onto the spotting surface by lowering or tapping the pin on the spotting surface so that the liquid transfers from the pin tip onto the spotting surface.
FIG. 1B of the accompanying drawings shows schematically a modified split pin design, also used for spotting in the prior art. Split pin 110 incorporates a reservoir 112 and has a blunt end so that liquid 111 extends beyond the pin tip. Liquid can be deposited onto a spotting surface by pressing the blunt end of the pin in contact with the spotting surface or by bringing the pin into very close proximity with the surface such that surface tension causes a drop to be transferred from pin to surface.
These pin designs have in common that they rely on capillary action to gain a reservoir of sample liquid sufficient for many spot depositions. This avoids having to dip into the well for each spot.
Most microarray pins in the prior art float vertically in a common head. They rest in the lowest position by gravity or spring biasing. The head tends to over travel by a small amount and the pins will lift in the head by the over travel.
Regardless of the pin design, spotting is carried out with the following basic steps. The pin is moved to above the well plate. The pin is dipped in a well of the well plate to retrieve some liquid. The pin carrying the liquid is moved over to above the spotting surface. The retrieved liquid is deposited from the pin onto the spotting surface, either with only one spot, or with several spots for a pin that carries a reservoir of sample liquid. The pin is moved back to the well plate to retrieve more liquid for further spotting.
FIGS. 2A to 2C of the accompanying drawings show the basic spotting process. In FIG. 2A, a pin 110 from a pin head 120 is lowered downwards, for example mechanically, to dip it into a well 112 of a well plate 114 and thereby retrieve an amount of liquid sample. In FIG. 2B, the liquid sample is deposited onto a spotting surface. In FIG. 2C, the pin is cleaned in a washing stage 118, typically after many spotting actions (i.e. FIG. 2A to FIG. 2B repeats) prior to commencing spotting with a different liquid sample.
Design effort has been concentrated on speeding up the head transit times so that the time taken between dipping in the well plate and spot deposition on the slide is reduced. As mentioned further above, the pins are also sometimes designed to use capillary action for storing a charge of liquid in the pin sufficient for depositing a number of spots. This also speeds up the spotting procedure by reducing the number of times the head needs to be traversed between the well plate and the slide.